Citations 2
Endoplasmic Reticulum Stress-Activated Transcription Factor ATF6α Requires the Disulfide Isomerase PDIA5 To Modulate Chemoresistance
Higa, Arisa, Taouji, Saı̈d , Lhomond, Stéphanie , Jensen, Devon, Fernández-Zapico, Martín E. , Simpson, Jeremy C. , Pasquet, Jean‐Max , Chevet, Éric , Schekman, Randy W. , Chevet, Eric
Molecular and Cellular Biology | March 18, 2014 | Volume: 34 | Issue: 10 | Pages: 1839-1849
Posttranscriptional Regulation of PER1 Underlies the Oncogenic Function of IREα
Pluquet, Olivier , Dejeans, Nicolas, Bouchecareilh, Marion , Lhomond, Stéphanie , Pineau, Raphaël , Higa, Arisa, Delugin, Maylis, Combe, Chantal, Loriot, Sandrine, Cubel, Gaëlle, Dugot‐Senant, Nathalie, Vital, Anne, Loiseau, Hugues , Gosline, Sara J.C. , Taouji, Saı̈d , Hallett, Michael , Anderson, Keith, Rosenbaum, Jean , Saltel, Frédéric , Fernández-Zapico, Martín E. , Chevet, Éric , Loriot, Sandrine, Sarkaria, Jann N. , Wu, Wenting , Rodríguez, Fausto J. , Chevet, Eric
Cancer Research | June 11, 2013 | Volume: 73 | Issue: 15 | Pages: 4732-4743
Abstract Growing evidence supports a role for the unfolded protein response (UPR) in carcinogenesis; however, the precise molecular mechanisms underlying this phenomenon remain elusive. Herein, we identified the circadian clock PER1 mRNA as a novel substrate of the endoribonuclease activity of the UPR sensor IRE1α. Analysis of the mechanism shows that IRE1α endoribonuclease activity decreased PER1 mRNA in tumor cells without affecting PER1 gene transcription. Inhibition of IRE1α signaling using either siRNA-mediated silencing or a dominant-negative strategy prevented PER1 mRNA decay, reduced tumorigenesis, and increased survival, features that were reversed upon PER1 silencing. Clinically, patients showing reduced survival have lower levels of PER1 mRNA expression and increased splicing of XBP1, a known IRE-α substrate, thereby pointing toward an increased IRE1α activity in these patients. Hence, we describe a novel mechanism connecting the UPR and circadian clock components in tumor cells, thereby highlighting the importance of this interplay in tumor development. Cancer Res; 73(15); 4732–43. ©2013 AACR.